Drug-Cytokine Interactions

  • Kerry B. GoralskiEmail author
  • Matthew A. Ladda
  • Jenna O. McNeil
Part of the Infectious Disease book series (ID)


There are many documented examples of altered drug disposition in human conditions that stimulate host cytokine responses. These include viral, bacterial, or parasitic infections, tissue injury, surgery, cancer, and autoimmune conditions. Interferons, interleukins 1 and 6, and tumor necrosis factor are the central mediators. These cytokines have been traditionally viewed with respect to their ability to suppress hepatic cytochrome P450 (CYP)-mediated drug detoxification. The potential result is a temporary conversion from a rapid or normal metabolizer to a poor metabolizer phenotype. Such aberrant drug handling has placed patients at risk for adverse drug responses to low therapeutic index, CYP-metabolized drugs like theophylline. It is now evident that drug-cytokine interactions are broader than once appreciated. They impact CYPs and drug transporter proteins ABCB1 (P-glycoprotein) in the liver, intestine, kidney, blood-brain barrier, placenta, and immune cells. Furthermore, the possibility that anti-cytokine biological therapies may precipitate drug-cytokine interactions is gaining increasing recognition. The consequences of drug-cytokine interactions are altered absorption, elimination, and/or cellular and tissue distribution of drugs. The outcomes can be negative or positive depending on the drug, the anatomical site of the interaction, and the therapeutic objectives. This chapter provides a historical overview of drug-cytokine interactions, discusses recent advances, and examines the clinical scenarios in which infections or inflammation might lead to abnormal drug handling and drug responses.


Interleukins Interferons Inflammatory Bowel Disease Cancer Autoimmune Vaccines Immunosuppression Surgery Placenta Tumor Necrosis Factor 


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Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  • Kerry B. Goralski
    • 2
    • 1
    Email author
  • Matthew A. Ladda
    • 2
  • Jenna O. McNeil
    • 3
  1. 1.Department of PharmacologyDalhousie UniversityHalifaxCanada
  2. 2.College of Pharmacy, Faculty of Health Professions, Dalhousie UniversityHalifaxCanada
  3. 3.Department of Family MedicineDalhousie UniversityHalifaxCanada

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